A Single Microglial Protein Controls Suite of Alzheimer’s Risk Genes

| Newsline

Genetic studies have turned up numerous genes linked to Alzheimer’s disease (AD), but in most cases, researchers have no idea how the genes raise or lower risk. A new genetic analysis now suggests that most of these genes act in the brain’s immune cells, microglia, not in neurons. A large group of researchers led by Alison Goate at the Icahn School of Medicine at Mount Sinai, New York, identified a protective genetic variant that delays when Alzheimer’s disease starts. The authors discovered that this variant lowered expression of the master microglial regulator PU.1. PU.1 regulates the expression of other microglial genes, controlling the cells’ survival and behavior. Notably, the authors found a huge number of AD risk genes among its downstream targets. Of 112 such genes they examined, 60 of them were expressed in microglia and controlled by PU.1. The results suggest that microglia, rather than neurons, may wield the most influence over AD pathogenesis.